Protective and pathogenic role of collagen subtypes genes COL4A3 and COL4A4 polymorphisms in the onset of keratoconus in South-Asian Pakistani cohort

Collagen sub-types have an important role in corneal structure and are reported to be an important genetic predictor for keratoconus (KC) development, therefore we assessed the association of collagen subtypes by screening non-synonymous polymorphisms of COL4A3 and COL4A4 in South-Asian (Pakistani) patients. METHODS: A total of 257 KC sporadic cases, gender and ethnicity matched 253 control individuals were screened for three non-synonymous single nucleotide polymorphisms (SNPs) rs55703767and rs10178458 in COL4A3 and rs2229814 and one synonymous SNP rs2228555 in COL4A4. The genotyping was done by Competitive Allele specific polymerase chain reaction (PCR) and the data were analyzed statistically. RESULTS: Among the studied SNPs, the COL4A3 rs55703767 GT genotype (dominant model (DM): odds ratio (OR) = 0.243, (95 %CI) = 0.16–0.36, p=>0.0001), and allele-G (OR = 0.35, 95 %CI = 0.26–0.48, p < 0.000)), showed protective association against KC development. While COL4A3 rs10178458 CT genotype (DM: OR = 2.11(95 %CI = 1.16–3.85), COL4A4 rs2229814 TT genotype (RM: OR = 147.778(95 %CI = 20.401–1070.439), (p > 0.05) and allele-T (OR = 2.351(95 %CI = 1.826–3.028), (p > 0.05); COL4A4 rs2228555 AG genotype (DM: OR = 2.370(95 %CI = 1.594–3.524) (<0.0001) and GG genotype (RM: OR = 2.347(95 %CI = 1.587–3.472), (p < 0.0001); and allele-G (OR = 2.024(95 %CI = 1.577–2.597), (p > 0.0001) were observed to be disease associated. CONCLUSION: COL4A3 rs10178458 and COL4A4 SNPs rs2229814 and rs2228555 were found to be pathogenic for KC, whereas COL4A3 rs55703767 was found to play a protective role against KC development in South-Asian (Pakistani) Cohort.